Biomedical subjects
M Kaito
Publications and source records attributed to M Kaito.
Case report: Alanine aminotransferase deficiency detected in a patient with chronic hepatitis C.
We report a case of alanine aminotransferase (ALT) deficiency in a 68-year-old Japanese female with chronic hepatitis C. The serum was positive for antibody to hepatitis C virus (HCV) and HCV-RNA. Liver biopsy showed histological evidence of chronic active hepatitis. The level of serum aspartate aminotransferase (sAST) was elevated, but sALT was extremely low. The patient was followed up for her serum aminotransferase levels for 1.5 years under the treatment with ursodeoxycholic acid. The low sALT level persisted during all the follow-up period. The ALT activity in liver tissue was also decreased. Based on these findings, ALT deficiency was suspected. sALT activity was also found to be low in her two sons. This latter finding suggests the hereditary character of this abnormality.
Flow cytometric analysis of IL-6 receptors on peripheral lymphocytes in patients with primary biliary cirrhosis.
Interleukin-6 receptors (IL-6R) and interleukin-1 receptors (IL-1R) on lymphocyte surfaces were analyzed, using flow cytometry and dye-labeled IL-6 and IL-1 beta, to examine the clinical and immunological significance of these receptors. Incubation of peripheral blood mononuclear cells in the presence of mitogen resulted in a remarkable increase of lymphocytes expressing the IL-6 and IL-1 beta receptors on the cell surface. The increase in lymphocytes bearing these cytokine receptors may reflect an increase in stimulated lymphocytes. When peripheral blood from patients with primary biliary cirrhosis (PBC) was examined for these receptors, the percentage of IL-6R positive cells was significantly higher in the patients than in healthy controls (P < 0.01). The increase in IL-6R positive cells was only significant for the T lymphocyte fraction (P < 0.01). No significant change in IL-1R was observed. There was a significant positive correlation between the percentage of IL-6R positive T lymphocytes and the titer of antimitochondrial antibody in patients with PBC. These findings concerning IL-6R may be noteworthy elucidating autoimmune etiological features of PBC.
Helicobacter pylori inhibits the secretory activity of gastric parietal cells in patients with chronic gastritis. An ultrastructural study.
BACKGROUND: Previous in vitro studies suggested that Helicobacter pylori may inhibit the acid secretion of gastric parietal cells. The aim of this study was to investigate ultrastructurally the influence of H. pylori infection on the gastric parietal cell function in vivo. METHODS: This study comprised 28 patients with chronic gastritis. Biopsy specimens were taken from the gastric body in all cases and examined by electron microscopy. Gastric parietal cells were counted in each ultrathin section and classified into secretory and non-secretory types. The pH of the gastric juice was also measured in all patients. RESULTS: The number of parietal cells in the secretory phase was significantly lower in H. pylori-infected (n = 16) patients than in those (n = 12) without H. pylori infection. The intragastric pH was significantly higher in patients with H. pylori-associated gastritis than in those without H. pylori infection. Parietal cells in secretory phase tended to decrease in proportion to the activity of the gastric mucosal inflammation. CONCLUSIONS: The results of this investigation suggests that H. pylori-associated gastritis is related to a decreased secretory activity of the gastric parietal cells.
[Searching for hepatitis C virus by immunoelectron microscopy and its morphology].
Many investigators have searched for the causative agent(s) of blood-borne non-A, non-B hepatitis in sera and liver from patients and experimental animals, and have reported various virus-like particles, morphologically resembling parvovirus, togavirus, picornavirus, hepadnavirus, paramyxovirus, papovavirus, retrovirus or bunyavirus. Despite extensive effort, none of these virus-like particles has been confirmed universally as an etiologic virus because of the absence of immunological identification. The frustration was solved by the success in cloning cDNA of the genome of hepatitis C virus (HCV), a major etiologic agent of human non-A, non-B hepatitis, in 1989, but the morphology of HCV remained in riddles. We attempted to visualize HCV by indirect immunogold electron microscopy, using specific antibodies to the putative HCV envelope 1 protein and succeeded in identifying HCV particle in HCV-RNA-rich plasma. Our study showed that HCV particles are 55-65 nm spherical particles with 6 nm fine surface spike-like projections, and have a 30-35 nm inner core.
[Ultrastructural feature of HCV particle as revealed by immunoelectron microscopy].
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[Non-A, non-B, non-C viral hepatitis].
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Hepatitis C virus particle detected by immunoelectron microscopic study.
To clarify the morphology of hepatitis C virus (HCV), an indirect immunogold electron microscopic study was carried out on two plasma samples with high HCV RNA titres using polyclonal and monoclonal antibodies specific to the putative HCV envelope protein. Spherical virus-like particles, 55 to 65 nm in diameter with spike-like projections, were found in 1.14 to 1.16 g/ml fractions after sucrose density gradient centrifugation. These particles were found only in HCV-infected blood donors and had morphological features similar to those of flaviviruses. Moreover, these particles specifically reacted with the polyclonal and monoclonal antibodies to the putative HCV envelope protein. This is the first known report in which the morphology of the HCV particle is clearly shown.
Appropriate interferon-alpha therapy for chronic hepatitis C: an assessment by quantitative changes in serum hepatitis C virus-RNA.
The antiviral effect of natural interferon (IFN)-alpha on chronic hepatitis C virus (HCV) infection was estimated by determining quantitative changes in serum HCV-RNA compared with the serum alanine aminotransferase (sALT) improvement; the relationships of responses to IFN according to the dose and period of IFN therapy were defined to determine an appropriate IFN therapy protocol. Twenty-two patients with chronic hepatitis C were given natural IFN-alpha and in 16 (72.7%) patients the viraemia was suppressed during therapy. Five (27.7%) of them sustained the disappearance of HCV-RNA for more than 6 months after therapy accompanied with a prolonged sALT improvement. Pre-treatment viraemia levels in 5 complete responders with "complete suppression" of viraemia were significantly lower than in 11 patients with a transient loss or a decline of HCV-RNA. A favorable antiviral response was closely associated with a high total dose of IFN-alpha and a long duration of IFN therapy.
Propagation of hepatitis A virus in a renal cell line JTC-12.P3 of cynomolgus monkey origin.
Human hepatitis A virus (HAV) derived from 10% HAV infected marmoset liver homogenate and faeces from acute hepatitis A was successfully propagated in vitro in a new cell line, JTC-12.P3. The cell line originated from the renal cortex of cynomolgus monkey which was adapted to growth in a serum free, protein free, chemically defined synthetic medium. Replication of the virus was followed by solid phase RIA, immunofluorescent staining, and immunoelectron microscopy. The propagation of HAV occurred over several passages, with the 1st and 2nd passages requiring at least 8 weeks each. However, with the increasing serial passage of virus, the period needed to detect it was shortened, suggesting the adaptation of HAV to the cells. The identity of the newly synthetized virus particles with HAV was established by immunoelectron microscopy and immunofluorescent blocking effect with human convalescent serum. The HAV propagated in JTC-12.P3 cells banded predominantly at a density of 1.32 g/cm3 in CsC1 gradient. The infected cells showed no specific signs of CPE. Ultrastructurally, clusters of virus particles 27 nm in diameter were observed mainly in the lysosomal vesicles and freely in crystalline array in the cytoplasm, too. Addition of 0.1% of various anti-HAV negative sera or of prostaglandin E1 to the culture medium caused accelerated propagation of HAV.
Quantitation and typing of serum hepatitis C virus RNA in patients with chronic hepatitis C treated with interferon-beta.
We quantified serum hepatitis C virus RNA titers and determined hepatitis C virus subtypes in chronic hepatitis C patients treated with interferon-beta to investigate relationships among serum ALT response, serum hepatitis C virus titer and hepatitis C virus subtype. Of 146 chronic hepatitis C patients who received interferon-beta therapy, 24 patients with sustained serum ALT normalization (complete responders) and 26 patients without serum ALT normalization (nonresponders) were randomly selected. Detection, typing and quantitation of hepatitis C virus were performed by means of the "single-tube" polymerase chain reaction method. Of the 24 complete responders, 21 (87.5%) became negative for hepatitis C virus RNA, whereas 21 (80.8%) of the 26 nonresponders remained positive. Hepatitis C virus infections with types I, II, III, IV, II + III and III + IV occurred in 0 (0%), 22 (51.2%), 10 (23.3%), 1 (2.3%), 7 (16.5%) and 3 (7.9%) patients, respectively. The mean pretreatment hepatitis C virus RNA titer of complete responders (0.4 +/- 2.0 x 10(4) CID50/ml) was significantly lower than that of nonresponders (3.8 +/- 4.5 x 10(4) CID50/ml) (p < 0.01). Regardless of HCV subtype, patients with more than 10(4) CID50/ml of HCV did not show serum ALT normalization, whereas complete serum ALT response was seen in most cases with less than 10(2) CID50/ml HCV. These results show that mixed infections with different hepatitis C virus subtypes appear to be more common than previously reported and that the pretreatment serum level of hepatitis C virus RNA is a more important predictor of outcome of interferon therapy than is virus genotype.
[An autopsy case of neoplastic angioendotheliomatosis with neurological symptoms accompanied with polymyositis].
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[Liver function tests: analysis of HAV antigen and antibody].
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Assessment of portosystemic shunt by summation of radioactivity during 201thallium chloride portal scintigraphy in patients with chronic liver disease.
BACKGROUND/AIMS: Portal scintigraphy is a useful non-invasive method for the determination of portosystemic shunts in patients with liver cirrhosis. Several procedures have been reported for its execution in clinical practice but most of them failed to show sufficient sensitivity for the diagnosis of portosystemic shunt. In the present study, we evaluated whether summation of radioisotope counts obtained during intrarectal or intraduodenal administration of 201thalium chloride is useful for increasing the diagnostic yield of porto-systemic shunts in patients with chronic liver disease. METHODOLOGY: Seven patients with chronic viral hepatitis and 8 with liver cirrhosis secondary to viral hepatitis were enrolled in this study. Following the conventional protocol, 201thalium chloride was administered per rectum and the 60-second-heart-to-liver uptake (conv-H/L-R) ratio was calculated after 20 min. Continuous measurement of the radioactivity signals during 20 min were also done and the summated heart-to-liver uptake (sum-H/L-R) ratio from the total radioactivity count were calculated. Measurement of the conventional heart-to-liver uptake (conv-H/L-D) ratio and the summated (sum-H/L-D) ratio were also done as described above after the intraduodenal administration of 201thalium chloride by endoscopy. RESULTS: All ratios (conv-H/L-R, conv-H/L-D, sum-H/D-R, sum-H/L-D) were significantly higher in patients with liver cirrhosis than in those with chronic hepatitis. Among all heart/liver ratios, only the sum-H/L-R ratio was significantly different between patients with and without esophageal varices. Serum hyaluronate level and other liver function tests were found to be significantly correlated with all heart-to-liver ratios, but they were more strongly correlated with the sum-H/D-R and sum-H/L-D ratios than with the conv-H/L-R and conv-H/L-D ratios. CONCLUSIONS: The results of this study showed that the heart-to-liver ratio calculated by summation of radioactivity is better than the conventional method for the diagnosis of portosystemic shunt in patients with chronic liver disease.